AIM: To evaluate the efficacy of amantadine plus interferonalpha and ribavirin in non-responder patients with chronic hepatitis C.METHODS: Twenty-six non-responder patients received the regimen of IFN-α-2a at a dose of 6 million units three times a week, 1 000-1 200 mg of ribavirin daily, and 200 mg of amantadine daily in divided doses over 48 wk. After the end of treatment, at the 72nd wk, a sustained viral response rate was determined.RESULTS: An early (after 12 wk of therapy) response was seen in 34.6% (9/26) of patients. Response rate at the 24th wk was 42.3% (11/26). End of treatment response (ETR) was 53.8% (14/26). Sustained viral response (SVR) was 42.3% (11/26). There was a statistically significant difference between 0 and 12 wk (P = 0.04), 0 and 24 wk (P = 0.01), 0 and 48 wk (P = 0.00), and 0 and 72 wk (P = 0.001). No patient had severe adverse effects during the treatment.CONCLUSION: Combination regimen of interferon-α,ribavirin and amantadine can enhance sustained viral response on IFN-α and ribavirin non-responder patients with HCV. Triple therapy with amantadine should be evaluated in further studies.